tbuckley/cabot-search huggingface dataset:
Underwater endoscopic mucosal resection with submucosal injection
Authors: Shintaro Hirata, Naoya Toyoshima, Hiroyuki Takamaru, Masayoshi Yamada, Nozomu Kobayashi, Takahiro Kozu, Yutaka Saito
Journal: Endoscopy (2022)

Underwater endoscopic mucosal resection (UEMR) is rapidly gaining popularity as a treatment that is easier than conventional EMR and endoscopic submucosal dissection (ESD) because submucosal injection is not necessary owing to the floating effect of tissue under water [1] [2]. However, it is currently unclear whether UEMR can ensure deep enough margins for pathological evaluation of early-stage colorectal cancer [3]. We present a case of modified UEMR with submucosal injection after underwater conditions have been established (UIEMR).
Fistula caused by cytomegalovirus enteritis hidden between swollen folds and detected by capsule enteroscopy
Authors: Satomi Shibata, Toshiro Iizuka, Ryoko Shimizuguchi, Akinari Takao, Shin-Ichiro Horiguchi
Journal: Endoscopy (2022)

A 72-year-old man with type 2 diabetes mellitus and receiving dialysis presented with a 6-month history of anemia (hemoglobin 5.6 g/dL). Upper and lower gastrointestinal endoscopies and computed tomography (CT) failed to identify the cause of the anemia. Small-intestine capsule endoscopy showed multiple ulcers with adherent blood ([Fig. 1]). After folds were separated during transanal enteroscopy, an ulcer was identified ([Fig. 2 a–c]). During an attempt to visualize the entire ulcer, another intestinal tract was discovered behind the ulcer ([Fig. 2 d]) ([Video 1]). Biopsy of the ulcer showed giant inclusion bodies in the granulation tissue that were confirmed immunohistochemically as cytomegalovirus (CMV)-positive cells ([Fig. 3]). The patient was diagnosed with CMV enteritis and treated with ganciclovir. At two months after treatment, his hemoglobin level had improved to 12.0 g/dL.
Acute iatrogenic gastric perforation during endoscopic ultrasound (EUS) for malignant biliary obstruction: intraoperative over-the-scope clip closure and EUS-guided biliary drainage with lumen-apposing metal stent
Authors: Roberto Di Mitri, Michele Amata, Filippo Mocciaro, Ambra Bonaccorso, Elisabetta Conte, Barbara Scrivo, Daniela Scimeca
Journal: Endoscopy (2022)

A 72-year-old woman presented with a 2-month history of jaundice and abdominal pain. A computed tomography scan revealed a large mass in the pancreatic head with dilated bile ducts. Endoscopic ultrasound (EUS)-guided fine-needle biopsy (FNB) and endoscopic retrograde cholangiopancreatography were scheduled for tissue acquisition and jaundice resolution.
Circumferential suture delivery method of polyglycolic acid sheets for gastric postendoscopic submucosal dissection ulcers
Authors: Yusuke Suzuki, Takashi Osoegawa, Masaru Kubokawa, Mitsuru Esaki, Yosuke Minoda, Haruei Ogino, Eikichi Ihara
Journal: Endoscopy (2022)

Polyglycolic acid (PGA) sheets with fibrin glue are reportedly effective in preventing post-procedural bleeding in gastric endoscopic submucosal dissection (ESD) [1] [2] [3] [4]. However, it is challenging to deliver and place the PGA sheet over the target ulcer in the correct position as the sheet is easily crumpled.
Single-operator cholangioscopy in a patient with prior pancreaticoduodenectomy
Authors: Michelle Baliss, Nicholas McDonald, Mohamed Abdallah, Mohammad Bilal
Journal: Endoscopy (2022)

A 64-year-old woman with a history of Gardner syndrome requiring classic pancreaticoduodenectomy for an ampullary adenoma 10 years prior presents for follow-up of adenomatous tissue at the hepaticojejunal anastomosis ([Fig. 1]) with an intraductal extension of adenomatous tissue ([Fig. 2]). She previously underwent endoscopic mucosal resection (EMR) of the adenomatous tissue and intraductal radiofrequency ablation (RFA) ([Fig. 3]). After EMR and RFA, the patient developed a stricture at the hepaticojejunal anastomosis. Subsequently, stricture dilations at the anastomosis were performed. The decision was made to perform cholangioscopy to evaluate for intraductal extension of adenomatous tissue ([Video 1]). A modified therapeutic upper endoscope (1T; GIF-1TH190 Olympus, Center Valley, Pennsylvania, United States) was used and advanced to the anastomosis. Cholangioscopy showed intraductal extension of adenomatous tissue. Cholangioscopy-directed biopsies were obtained. Pathology revealed tubular adenoma without high grade dysplasia. Repeat intraductal RFA is planned.
“Our plan for patients”—neither bold nor a plan
Authors: Martin Marshall
Journal: BMJ (2022)

There might have been some patients who were pleased to see headlines such as "An end to the 8am Glastonbury-esque scramble for GP appointments" that heralded Thérèse Coffey's first major announcement since taking up the health and social care portfolio in the new Cabinet, but I suspect most were underwhelmed.
Combination of Astrogliosis and Phosphorylated Tau for the Preclinical Diagnosis of Alzheimer Disease Using 3-Dimensional Stereotactic Surface Projection Images With 18F-THK5351
Authors: Etsuko Imabayashi, Yuji Saitoh, Tadashi Tsukamoto, Masuhiro Sakata, Harumasa Takano
Journal: Clinical Nuclear Medicine (2022)

The Alzheimer disease (AD) brain is characterized microscopically by the presence of extracellular amyloid plaques and intraneuronal neurofibrillary tangles consisting of phosphorylated tau aggregations. 18 F-THK5351 is a first-generation PET tau tracer that also binds to monoamine oxidase B, which represents astrogliosis, and is useful to evaluate some non-AD neurodegenerative disorders. We examined the utility of 18 F-THK5351 in preclinical AD using 3-dimensional stereotactic surface projection images optimized for its pathological accumulation by comparison with a normal dataset. By using this 18 F-THK5351 3-dimensional stereotactic surface projection procedure, which can evaluate phosphorylated tau and neuroinflammation, we could diagnose preclinical AD effectively.
The proto-oncogene TCL1A deregulates cell cycle and genomic stability in CLL
Authors: Johanna Stachelscheid, Qu Jiang, Christoph Aszyk, Kathrin Warner, Nadine Bley, Tony Müller, Olga Vydzhak, Konstantinos Symeonidis, Giuliano Crispatzu, Petra Mayer, Stuart James Blakemore, Gudrun Goehring, Sebastian Newrzela, Stephanie Hippler, Sandra Robrecht, Karl-Anton Kreuzer, Christian Pallasch, Marcus Krüger, Axel Lechner, Kirsten Fischer, Stephan Stilgenbauer, Dirk Beutner, Michael Hallek, Daniel Auguin, Stefan Hüttelmaier, Johannes Bloehdorn, Elena Vasyutina, Marco Herling
Journal: Blood (2022)

Upregulation of the proto-oncogene T-cell leukemia/lymphoma 1A (TCL1A) is causally implicated in various B-cell and T-cell malignancies. High-level TCL1A correlates with aggressive disease features and inferior clinical outcomes. However, the molecular and cell biological consequences of, particularly nuclear, TCL1A are not fully elucidated. We observed here in mouse models of subcellular site-specific TCL1A-induced lymphomagenesis that TCL1A exerts a strong transforming impact via nuclear topography. In proteomic screens of TCL1A-bound molecules in chronic lymphocytic leukemia (CLL) cells and B-cell lymphoma lines, we identified regulators of cell cycle and DNA repair pathways as novel TCL1A interactors, particularly enriched under induced DNA damage and mitosis. By functional mapping and in silico modeling, we specifically identified the mitotic checkpoint protein, cell division cycle 20 (CDC20), as a direct TCL1A interactor. According to the regulatory impact of TCL1A on the activity of the CDC20-containing mitotic checkpoint and anaphase-promoting complexes during mitotic progression, TCL1A overexpression accelerated cell cycle transition in B-cell lymphoma lines, impaired apoptotic damage responses in association with pronounced chromosome missegregation, and caused cellular aneuploidy in Eμ-TCL1A mice. Among hematopoietic cancers, CDC20 levels seem particularly low in CLL. CDC20 expression negatively correlated with TCL1A and lower expression marked more aggressive and genomically instable disease and cellular phenotypes. Knockdown of Cdc20 in TCL1A-initiated murine CLL promoted aneuploidy and leukemic acceleration. Taken together, we discovered a novel cell cycle-associated effect of TCL1A abrogating controlled cell cycle transition. This adds to our concept of oncogenic TCL1A by targeting genome stability. Overall, we propose that TCL1A acts as a pleiotropic adapter molecule with a synergistic net effect of multiple hijacked pathways.
Rising cost of living is worsening NHS workforce crisis and workload
Authors: Ingrid Torjesen
Journal: BMJ (2022)

<h3>Objective</h3> Community-based reports regarding the association between the estimated glomerular filtration rate (eGFR) and dementia risk show conflicting results. The aim of this study is to investigate the links among kidney function, kidney function decline, and dementia incidence. <h3>Methods</h3> We analyzed the association of eGFR with the risk of dementia (defined as a new dementia diagnosis or initiation of dementia treatments) among 329,822 residents of Stockholm who accessed health care during 2006 to 2011, were ≥65 years of age, had no history of dementia, or underwent kidney replacement therapy. We also estimated the rate of eGFR decline among 205,622 residents with repeated eGFR measurements during the first year of observation and investigated its association with subsequent dementia risk. <h3>Results</h3> We detected 18,983 cases of dementia (5.8% of participants) over a median follow-up of 5 years. Dementia incidence rates were progressively higher with lower eGFR: from 6.56/1,000 person-years in those with eGFR of 90 to 104 mL/min to 30.28/1,000 person-years in those with eGFR &lt;30 mL/min. After multivariable adjustment, lower eGFR was associated with a higher dementia risk (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.54–1.91 in eGFR 30–59 mL/min; HR 2.62, 95% CI 1.91–3.58 in eGFR &lt;30 mL/min) compared with eGFR of 90 to 104 mL/min. A steeper decline in eGFR (decline &gt;2 mL/min/1.73 m<sup>2</sup>/y) within 1 year was associated with higher dementia risk. Risk magnitudes were stronger for vascular dementia than for Alzheimer dementia. As many as 10% (95% CI 6%–14%) of dementia cases could be attributed to eGFR &lt;60 mL/min/1.73 m<sup>2</sup>, a proportion higher than that attributed to other dementia risk factors such as cardiovascular disease and diabetes. <h3>Conclusions</h3> Both lower kidney function and steeper kidney function decline are associated with the development of dementia.
Financial Hardship in Adult Survivors of Childhood Cancer in the Era After Implementation of the Affordable Care Act: A Report From the Childhood Cancer Survivor Study
Authors: Paul C. Nathan, I-Chan Huang, Yan Chen, Tara O. Henderson, Elyse R. Park, Anne C. Kirchhoff, Leslie L. Robison, Kevin Krull, Wendy Leisenring, Gregory T. Armstrong, Rena M. Conti, Yutaka Yasui, K. Robin Yabroff
Journal: Journal of Clinical Oncology (2022)

To estimate the prevalence of financial hardship among adult survivors of childhood cancer compared with siblings and identify sociodemographic, cancer diagnosis, and treatment correlates of hardship among survivors in the era after implementation of the Affordable Care Act.
Elevated C-Reactive Protein and Subsequent Patient-Reported Cognitive Problems in Older Breast Cancer Survivors: The Thinking and Living With Cancer Study
Authors: Judith E. Carroll, Zev M. Nakamura, Brent J. Small, Xingtao Zhou, Harvey J. Cohen, Tim A. Ahles, Jaeil Ahn, Traci N. Bethea, Martine Extermann, Deena Graham, Claudine Isaacs, Heather S.L. Jim, Paul B. Jacobsen, Brenna C. McDonald, Sunita K. Patel, Kelly Rentscher, James Root, Andrew J. Saykin, Danielle B. Tometich, Kathleen Van Dyk, Wanting Zhai, Elizabeth C. Breen, Jeanne S. Mandelblatt
Journal: Journal of Clinical Oncology (2022)

To examine longitudinal relationships between levels of C-reactive protein (CRP) and cognition in older breast cancer survivors and noncancer controls.
Assembly of von Willebrand factor tubules with in vivo helical parameters requires A1 domain insertion
Authors: Gabriel Javitt, Noa Yeshaya, Lev Khmelnitsky, Deborah Fass
Journal: Blood (2022)

The von Willebrand factor (VWF) glycoprotein is stored in tubular form in Weibel-Palade bodies (WPBs) before secretion from endothelial cells into the bloodstream. The organization of VWF in the tubules promotes formation of covalently linked VWF polymers and enables orderly secretion without polymer tangling. Recent studies have described the high-resolution structure of helical tubular cores formed in vitro by the D1D2 and D'D3 amino-terminal protein segments of VWF. Here we show that formation of tubules with the helical geometry observed for VWF in intracellular WPBs requires also the VWA1 (A1) domain. We reconstituted VWF tubules from segments containing the A1 domain and discovered it to be inserted between helical turns of the tubule, altering helical parameters and explaining the increased robustness of tubule formation when A1 is present. The conclusion from this observation is that the A1 domain has a direct role in VWF assembly, along with its known activity in hemostasis after secretion.
Young women and anal sex: education should minimise risk
Authors: Michael D E Goodyear
Journal: BMJ (2022)

Identifying the features of population responses that are relevant to the amount of information encoded by neuronal populations is a crucial step toward understanding population coding. Statistical features, such as tuning properties, individual and shared response variability, and global activity modulations, could all affect the amount of information encoded and modulate behavioral performance. We show that two features in particular affect information: the modulation of population responses across conditions (population signal) and the inverse population covariability along the modulation axis (projected precision). We demonstrate that fluctuations of these two quantities are correlated with fluctuations of behavioral performance in various tasks and brain regions consistently across 4 monkeys (1 female and 1 male <i>Macaca mulatta</i>; and 2 male <i>Macaca fascicularis</i>). In contrast, fluctuations in mean correlations among neurons and global activity have negligible or inconsistent effects on the amount of information encoded and behavioral performance. We also show that differential correlations reduce the amount of information encoded in finite populations by reducing projected precision. Our results are consistent with predictions of a model that optimally decodes population responses to produce behavior. <b>SIGNIFICANCE STATEMENT</b> The last two or three decades of research have seen hot debates about what features of population tuning and trial-by-trial variability influence the information carried by a population of neurons, with some camps arguing, for instance, that mean pairwise correlations or global fluctuations are important while other camps report opposite results. In this study, we identify the most important features of neural population responses that determine the amount of encoded information and behavioral performance by combining analytic calculations with a novel nonparametric method that allows us to isolate the effects of different statistical features. We tested our hypothesis on 4 macaques, three decision-making tasks, and two brain areas. The predictions of our theory were in agreement with the experimental data.
Authors’ reply to Goodyear, Merli and colleagues, and Waters and Dewsnap
Authors: Tabitha Gana, Lesley M Hunt
Journal: BMJ (2022)

Freshly isolated hepatocytes are widely accepted as the “gold standard” for providing reliable data on drug uptake across the sinusoidal (basolateral) membrane. However, the suitability of freshly isolated hepatocytes in suspension to assess efflux by canalicular (apical) proteins or predict biliary excretion in the intact organ is unclear. After collagenase digestion, hepatocytes rapidly lose polarity, but localization of canalicular transport proteins in the first few hours after isolation has not been well characterized. In this study, immunostaining and confocal microscopy have provided, for the first time, a detailed examination of canalicular transport protein localization in freshly isolated rat hepatocytes fixed within 1 h of isolation and in cells cultured for 1 h. Organic anion transporting polypeptide 1a1 (Oatp1a1) was expressed in all hepatocytes and distributed evenly across the basolateral membrane; there was no evidence for colocalization of Oatp1a1 with P-glycoprotein (P-gp) or multidrug resistance-associated protein 2 (Mrp2). In contrast, P-gp and Mrp2 expression was lower than Oatp1a1 and confined to junctions between adjacent cells, intracellular compartments, and “legacy” network structures at or near the cell surface. P-gp and Mrp2 staining was more predominant in regions adjacent to former canalicular spaces, identified by zonula occludens-1 staining. Functional analysis of rat hepatocytes cultured for 1 h demonstrated that the fluorescent anion and Mrp2 substrate, 5-(and-6)-carboxy-2′,7′-dichlorofluorescein (CDF), accumulated in cellular compartments; compartmental accumulation of CDF was sensitive to (<i>E</i>)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-[[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK571, Mrp inhibitor) and was not observed in hepatocytes isolated from Mrp2-deficient rats. Drug efflux from freshly isolated hepatocytes as an estimate of apical efflux/biliary excretion would give an inaccurate assessment of true apical elimination and, as such, should not be used to make in vivo extrapolations.
Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation
Authors: Sudeep Ghimire, Nicole M. Cady, Peter Lehman, Stephanie R. Peterson, Shailesh K. Shahi, Faraz Rashid, Shailendra Giri, Ashutosh K. Mangalam
Journal: Gut Microbes (2022)

The etiopathogenesis of multiple sclerosis (MS) is strongly affected by environmental factors such as diet and the gut microbiota. An isoflavone-rich (ISO) diet was previously shown to reduce the severity of MS in the animal model experimental autoimmune encephalomyelitis (EAE). Translation of this concept to clinical trial where dietary isoflavones may be recommended for MS patients will require preliminary evidence that providing the isoflavone-rich diet to people with MS (PwMS) who lack phytoestrogen-metabolizing bacteria has beneficial effects. We have previously shown that the gut microbiota of PwMS resembles the gut microbiota of mice raised under a phytoestrogen-free (phyto-free) diet in that it lacks phytoestrogen-metabolizing bacteria. To investigate the effects of phytoestrogens on the microbiota inflammatory response and EAE disease severity we switched the diet of mice raised under a phyto-free (PF) diet to an isoflavone-rich diet. Microbiota analysis showed that the change in diet from one that is ISO to one that is PF reduces beneficial bacteria such as Bifidobacterium species. In addition we observed functional differences in lipopolysaccharide (LPS) biosynthesis pathways. Moreover LPS extracted from feces of mice fed an ISO diet induced increased production of anti-inflammatory cytokines from bone marrow-derived macrophages relative to fecal-LPS isolated from mice fed a PF diet. Eventually mice whose diet was switched from a PF diet to an ISO diet trended toward reduced EAE severity and mortality. Overall we show that an isoflavone-rich diet specifically modulates LPS biosynthesis of the gut microbiota imparts an anti-inflammatory response and decreases disease severity.
The Maintenance of Competence Program of the Royal College of Physicians and Surgeons of Canada
Authors: John T. Parboosingh
Journal: JAMA (1993)

THE GOAL of the Maintenance of Competence (MOCOMP) Program of the Royal College of Physicians and Surgeons of Canada (RCPSC) is to motivate specialists to take a curriculum approach to managing their continuing medical education (CME). In Canada, "specialist" applies to all physicians who are certified fellows of the RCPSC. Of the 54 medical specialty societies in Canada, 10 are participating in the MOCOMP project and another five are negotiating participation. The MOCOMP is completing the second year of its pilot phase; on September 13, we should address all 54 specialty societies and hope that they, too, will join the program. In the MOCOMP Program, individual specialists set up a personal CME curriculum that includes an objective assessment of their practice needs, use of self-directed (eg, journal reading, literature retrieval) and group CME resources (eg, rounds, conferences) selected on the basis of a credit system that rewards participation in practice-based
Role of platelets in hepatic allograft preservation injury in the rat
Authors: Robert Cywes, Marian A. Packham, Linda Tietze, Juan R. Sanabria, Robert P. C. Harvey, James M. Phillips, Steven M. Strasberg
Journal: Hepatology (1993)

Cold preservation of liver allografts injures hepatic sinusoidal lining cells. This injury is exacerbated on reperfusion, in part because of adhesion of leukocytes. Platelets also adhere to activated endothelial surfaces. In this study we examined the role of platelets in preservation injury. Our specific aim was to determine whether the degree of platelet adhesion on reperfusion of preserved rat livers was related to duration of cold or warm ischemia and whether platelet adhesion resulted in injury to allografts. We also examined the effect of prior activation of platelets on adhesion and injury. Rat livers were preserved at 1° C for different time periods in University of Wisconsin solution and then reperfused for 3 hr on the isolated perfused rat liver system with Krebs-Henseleit solution to which unactivated isolated rat platelets were added. Other livers were rewarmed before reperfusion or reperfused with activated platelets. Platelets were lost from the circulation in all studies; the percentage reduction of circulating platelets was dependent on the length of preservation. The initial platelet concentration did not affect the rate of reduction of platelets in the circuit. Rewarming before reperfusion increased platelet adherence, and prior activation also increased adherence. With electron microscopy we determined that platelets adhered in small aggregates to endothelial cells or endothelial cell remnants. Adherent platelets appeared more activated and contained fewer granules than did unperfused platelets. Liver injury as measured by release of transaminases into perfusate was worsened by longer periods of cold preservation and by addition of rewarming to the protocol. The presence of platelets under these circumstances aggravated injury. Prior activation of platelets also increased the extent of injury. These studies show that platelets have an important role in cold preservation-reperfusion injury. (HEPATOLOGY 1993;18:635-647.)
Myocardial Infarction with Nonobstructive Coronary Arteries
Authors: H.R. Reynolds, N.R. Smilowitz
Journal: Annual Review of Medicine (2022)

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is an important subtype of myocardial infarction (MI) that occurs in approximately 6–8% of patients with spontaneous MI who are referred for coronary angiography. MINOCA disproportionately affects women, but men are also affected. Pathogenesis is more variable than in MI with obstructive coronary artery disease (MI-CAD). Dominant mechanisms include atherosclerosis, thrombosis, and coronary artery spasm. Management of MINOCA varies based on the underlying mechanism of infarction. Therefore, systematic approaches to diagnosis are recommended. The combination of invasive coronary angiography, multivessel intracoronary imaging, provocative testing for coronary spasm, and cardiac magnetic resonance imaging provides the greatest diagnostic yield. Current clinical practice guidelines for the secondary prevention of MI are based largely on data from patients with MI-CAD. Thus, optimal medications after MINOCA are uncertain. Clinical trials focused on the treatment of patients with MINOCA are urgently needed to define optimal care.